Since 1971, there has been accumulating evidence that povaviruses (viruses of the SV40-polyoma subgroup of papovaviruses) are pathogenic for humans, particularly in immunologically compromised persons. The two newly recognized viruses of this subgroup, BK virus (bkv) and JC virus (JCV), commonly infect children, but may be re-activated in later years: BKV as a urinary tract infection in renal allograft recipients and JCV affecting the central nervous system and leading to progressive multifocal leukoencephalopathy (PML). SV40 has been isolated from PML brains and from a melanoma metastasis. The projected studies aim at defining the role of these viruses in human disease, including cancer. Methods will be developed which will lead to quicker identification of these viruses. Patients with primary immune deficiency diseases will be studied to determine if the course of virus infection and patterns of virus excretion in this group are atypical. Renal allograft recipients will be studied to investigate the probable role of virus activation in rejection episodes. Attempts will be made to determine if primary infection with these viruses is associated with a urinary tract illness. Virus-induced tumors in hamsters will be studied mainly to evaluate the best methods for investigation of virus etiology of human tumors. Cells from a wide variety of human tumors will be screened for povavirus antigens. Tumor cells which have virus-specified antigens will be investigated in detail to determine the identity of the virus. Epidemiological, clinical, and laboratory studies will be performed to assess the significance of the virus genome in tumor cells. Newly recognized povaviruses of non-human origin will be studied for their antigenic relatedness to the human povaviruses.